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Subsequent Event Risk in Individuals With Established Coronary Heart Disease
Riyaz S Patel1,2, Vinicius Tragante3, Amand F Schmidt1,3
1Institute of Cardiovascular Science (R.S.P., A.F.S., L.J.H., K.D., J.D., A.D.H., F.W.A), Faculty of Population Health Science, University College London, United Kingdom.
Insights
The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium identifies genetic risk factors for secondary heart events. This global effort uses federated analysis to improve risk prediction and find new treatments for patients with existing coronary heart disease.
Area of Science:
- Cardiovascular Genetics
- Epidemiology
- Biomarker Discovery
Background:
- The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was formed to discover and validate genetic variants and biomarkers for subsequent coronary heart disease (CHD) events in individuals with established CHD.
- It aims to improve risk prediction and identify novel therapeutic targets for secondary prevention.
Purpose of the Study:
- To facilitate the discovery and validation of genetic variants and biomarkers associated with the risk of subsequent CHD events.
- To improve residual risk prediction in individuals with established CHD.
- To identify novel drug targets for secondary prevention of cardiovascular events.
Main Methods:
- The GENIUS-CHD consortium comprises 57 studies across 18 countries, including 185,614 participants with a history of acute coronary syndrome or stable CHD.
- Biological samples were collected, and participants were followed prospectively for subsequent cardiovascular events.
- A federated analysis approach was employed for initial feasibility analyses.
Main Results:
- Initial federated analyses confirmed expected associations between age, male sex, and smoking with the risk of subsequent CHD death or myocardial infarction.
- Hazard ratios indicated increased risk with age (1.15 per 5-year increase), male sex (1.17), and smoking (1.43).
- Differing associations were observed for other individual and composite cardiovascular endpoints.
Conclusions:
- GENIUS-CHD is a global collaboration focused on understanding genetic and non-genetic determinants of subsequent event risk in patients with established CHD.
- The consortium has demonstrated the feasibility and reliability of a federated analysis approach.
- Future plans include initiating novel hypothesis testing and supporting replication/validation analyses for other researchers.
Background:
The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.
Methods:
The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.
Results:
Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.
Conclusions:
GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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